This application is a 371 of PCT/EP01/10765 filed Sep. 18, 2001.
This invention relates generally to the encapsulation of active substances and, more particularly, to hydrophobicized powders consisting of micro- and/or nanocansules, to a process for their production and to their use in cosmetic and pharmaceutical preparations.
“Microcapsules” are understood to be spherical aggregates with a diameter of about 1 to about 5,000 μm and “nanocapsules” similar aggregates with a diameter below 1 μm which contain at least one solid or liquid core surrounded by at least one continuous membrane. More precisely, they are finely dispersed liquid or solid phases coated with film-forming polymers, in the production of which the polymers are deposited onto the material to be encapsulated after emulsification and coacervation or interfacial polymerization. In another process, liquid active principles are absorbed in a matrix (“microsponge”) which, as microparticles, may be additionally coated with film-forming polymers. Transitions between micro- or nanoparticles in which substances are encapsulated in a membrane (reservoir system) and micro- or nanoparticles in which the active substances are dispersed or dissolved in the carrier matrix (matrix system) arise out of the particular production process. Besides single-core microcapsules, there are also multiple-core aggregates, also known as microspheres, which contain two or more cores distributed in the continuous membrane material. In addition, single-core or multiple-core microcapsules may be surrounded by an additional second, third etc. membrane. The membrane may consist of natural, semisynthetic or synthetic materials. Natural membrane materials are, for example, gum arabic, agar agar, agarose, maltodextrins, alginic acid and salts thereof, for example sodium or calcium alginate, fats and fatty acids, cetyl alcohol, collagen, chitosan, lecithins, gelatin, albumin, shellac, polysaccharides, such as starch or dextran, polypeptides, protein hydrolyzates, sucrose and waxes. Semisynthetic membrane materials are inter alia chemically modified celluloses, more particularly cellulose esters and ethers, for example cellulose acetate, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose and carboxymethyl cellulose, and starch derivatives, more particularly starch ethers and esters. Synthetic membrane materials are, for example, polymers, such as polyacrylates, polyamides, polyvinyl alcohol or polyvinyl pyrrolidone.
Examples of known microcapsules are the following commercial products (the membrane material is shown in brackets) Hallcrest Microcapsules (gelatin, gum arabic), Coletica Thalaspheres (maritime collagen), Lipotec Millicapseln (alginic acid, agar agar), Induchem Unispheres (lactose, microcrystalline cellulose, hydroxypropylmethyl cellulose), Unicerin C30 (lactose, microcrystalline cellulose, hydroxypropylmethyl cellulose), Kobo Glycospheres (modified starch, fatty acid esters, phospholipids), Softspheres (modified agar agar) and Kuhs Probiol Nanospheres (phospholipids).
Reference is also made in this connection to German patent application DE 19712978 A1 (Henkel) which describes chitosan microspheres obtained by mixing chitosans or chitosan derivatives with oil components and introducing the resulting mixtures into alkalized surfactant solutions. In addition, the use of chitosan as an encapsulating material for tocopherol is known from German patent application DE 19756452 A1 (Henkel). Patent Application EP 99 122 906 relates to microcapsules with mean diameters of 0.1 to 500, preferably 25 to 250 and more particularly 50 to 100 μm which consist of a membrane material of starch and chitosans.
The micro- and nanocapsules produced in different ways may then be converted into a powder-form end product by drying in the form of freeze-drying or fluidized-bed drying or by the removal of water (FR 2775441 B1 and EP 99 122 906). In many cases, however, further processing such as this involves complicated, expensive and time-consuming processes and often leads to premature destruction of the micro- and nanocapsules. Since the microcapsules have hydrophilic surface properties, they are often difficult to incorporate in lipophilic preparations.
So-called dispersion aids (colloidal silicon), which contribute towards optimizing the flowability of the powders, are only used after the powders have been isolated. An advantage of similar formulations used in cosmetics is the regulation of fat-absorbing as opposed to drying-out properties (U.S. Pat. No. 5,948,417). U.S. Pat. No. 5,356,617 describes how the unsatisfactory processing of hydrophilic pigments can be improved by the production of microparticles from organic polymer, inorganic pigments and a binder. Even oily substances and lipophilic carriers can be converted for better processing into powders which are then readily incorporated in cosmetic preparations (EP 0 659 403 and U.S. Pat. No. 4,164,563). However, the use of micro- and/or nanocapsules raises greater processing problems.
The active principles are released from the microcapsules by mechanical, thermal, chemical or enzymatic destruction of the membrane or by diffusion, normally during the use of the preparations containing the microcapsules. Disadvantages in this regard are that the microcapsules do not allow controlled release of the active principles from their interior at all or only to an inadequate extent and that the capsules lack stability in the presence of surfactants, especially anionic surfactants, salts or mechanical loads.
Accordingly, the problem addressed by the present invention was to provide a stable powder-form formulation consisting of hydrophilically encapsulated active substances and auxiliaries which would be easy to incorporate in water-free formulations. The powder would be produced by simple, economical processes. In addition, release behavior would be able to be controlled and the formulation would be guaranteed a long storage life.